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NCT Number: NCT06514560

OPTImizing MIltefosine Treatment for Cutaneous LEISHmaniasis Patients

While there are indications that 28 days of miltefosine is not sufficient for treating CL by L. aethiopica, a better understanding of what happens in terms of parasite clearance and drug dosing is lacking. In this study, longitudinal measurements of parasite and drug concentrations during treatment are done to monitor parasite kinetics as well as pharmacokinetics. This data will be crucial to provide more information on duration and dosing of miltefosine in CL patients globally, and in Ethiopia and pediatric patients in particular.

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Key information

Conditions

Cutaneous Leishmaniases Euglenozoa Infections Infections Leishmaniasis Leishmaniasis, Cutaneous Parasitic Diseases Protozoan Infections Skin Diseases Skin Diseases, Infectious Skin Diseases, Parasitic Skin and Connective Tissue Diseases Vector Borne Diseases

Age range

2 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Africa Leprosy, Tuberculosis, Rehabilitation and Training (ALERT) Hospital

Addis Ababa, Ethiopia

Location status: Recruiting

Location contact

Shimelis Negusse, MD

CONTACT

[email protected]

09 11642060 ext. +251

About this study

In this project, parasite dynamics and miltefosine pharmacokinetics in the skin and blood during routine durations of miltefosine treatment (4-8 weeks) are studied with the aim to provide evidence to optimize miltefosine dosing for treatment of CL. By also studying these factors in children who get allometric miltefosine dosing, data which can be used to adapt the current allometric dosing scheme specifically to children with CL will be produced. Exploratory objectives will look into searching for more objective outcome assessment measures, resistance, helminth infection and nutritional status as potential factors affecting treatment response.

Who can participate

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Clinical or parasitological (microscopy or PCR) confirmation of leishmaniasis
  • Age >2
  • Clinical decision to start miltefosine treatment as systemic treatment
  • In case of females of child-bearing age: willing to take contraceptive for 6 months (parenteral or IUD or implant)
  • Willing and able to provide informed consent
  • Willing to be hospitalized for the duration of treatment

Exclusion criteria

  • Currently on treatment or having received modern treatment for leishmaniasis in the last 3 months
  • Pregnant (pregnancy test at D0) or breastfeeding
  • Unlikely to come for follow-up visits
  • Abnormal lab values Hemoglobin <5.0g/100mL Platelets <50 x 10^9/L White blood count <1 x 10^9/L ASAT/ALAT >3x upper normal range Creatinine above the normal limit

Treatment and study plan

Miltefosine

Drug

Miltefosine will be prescribed by the treating physician for a minimum of 4 weeks. If treatment response is not sufficient, treatment extension could be decided by the treating physician up to 8 weeks

Primary outcomes

  1. Miltefosine plasma concentrations - Area under the plasma concentration versus time curve (AUC)

    Time frame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180

    Determined by LC-MS/MS, miltefosine pharmacokinetics are assessed through calculation of the area under the plasma concentration-time curve from start of treatment until end of treatment (AUC0-EoT), stratified by whether patients received allometric dosing or not.

  2. Miltefosine plasma concentrations - Maximum plasma concentration (Cmax)

    Time frame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180

    Determined by LC-MS/MS, stratified by whether patients received allometric dosing or not.

  3. MIltefosine plasma concentrations - Time of maximum concentration (Tmax)

    Time frame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180

    Determined by LC-MS/MS, stratified by whether patients received allometric dosing or not.

Secondary outcomes

  1. Parasite kinetics in blood and skin

    Time frame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180

    To determine parasite kinetics in terms of Ct-values in blood and skin (microbiopsy sample) measured by quantitative PCR

  2. Adapted allometric dosing scheme specifically for children with CL

    Time frame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180

    Population PK and PK-PD analysis of the relationship between miltefosine exposure and parasite kinetics will be done at UU, based on results from miltefosine plasma concentrations. Structural pharmacokinetic modelling will be used to develop and simulate alternative dosing schemes for children with CL, using Monte Carlo simulations.

  3. Treatment outcomes of patients on miltefosine treatment

    Time frame: Day 28, day 90 and day 180

    Clinical cure rate determined by complete flattening, complete reepithelization and absence of erythema, crustation, and swelling

  4. Assess safety of miltefosine

    Time frame: Day 28

    Side-effects: number and proportion of patients with adverse events

Other outcomes

  1. To explore optimization of outcome assessment using a 3D scanner

    Time frame: Day 28, Day 90, Day 180

    Machine learning models will be built to explore accuracy (% correctly predicted) of 3D scanning models to predict clinical outcomes.

  2. To explore whether nutritional status in CL patients is related to treatment outcomes

    Time frame: Nutritional status at Day 0, outcome at Day 90/Day 180

    Logistic regression models will be made with clinical cure/no cure as outcome, and nutritional status measured through Z-scores as predictor.

  3. To explore whether helminth infection in CL patients is related to treatment outcomes

    Time frame: Helminth infection at Day 0, outcome at Day 90/Day 180

    Logistic regression models will be made with clinical cure/no cure as outcome, and helminth infection (determined as present/not present by wet mount stool exam) as predictor.

  4. To explore sequencing to detect intrinsic and acquired resistance markers for miltefosine

    Time frame: Day 0, Day 28/Day 42/Day 56, unscheduled visit

    Whole genome sequencing will be done at AHRI to check for intrinsic (before treatment samples) and acquired resistance (relapse and end of treatment samples).

  5. To explore skin tissue miltefosine concentrations

    Time frame: Day 28/Day 42/Day 56

    Measured by LC-MS/MS

Study contacts

Contact information is provided by the study sponsor or research team.

Shimelis Nigusse, MD

CONTACT

[email protected]

0911642060

Sponsors and collaborators

Lead sponsor

Institute of Tropical Medicine, Belgium

Other

Collaborators

  • Alert Hospital, Ethiopia
  • Armauer Hansen Research Institute, Ethiopia
  • The Netherlands Cancer Institute
  • Uppsala University

Registry information

Acronym: OPTIMILEISH

Important dates

Study start
2024
Primary completion
2025
Study completion
2026
First posted
Jul 23, 2024
Registry last updated
Jul 23, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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